Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Epoprostenol 1.5 mg powder for solution for infusion
⚠ This medicine appears to have been discontinued
The electronic medicines compendium (emc) no longer publishes a Summary of Product Characteristics for this product, which usually means it is no longer marketed in the UK. The patient leaflet below is kept for reference, but the product may not be available.
If you were prescribed this medicine, other products containing Epoprostenol sodium may still be available. Do not stop your treatment — ask your pharmacist or GP what to use instead.
What it is and what it is used for
for
Epoprostenol contains the active substance epoprostenol which belongs to a group of medicines called prostaglandins, which stop blood from clotting and widen the blood vessels. Epoprostenol is used to treat a lung condition called 'pulmonary arterial hypertension'. This is where the pressure is high in the blood vessels in the lungs. Epoprostenol widens the blood vessels to lower the blood pressure in the lungs. Epoprostenol is also used to prevent blood clotting during kidney dialysis in emergency situations when heparin cannot be used.
2.
What you need to know before you take it
e Epoprostenol
Do NOT use Epoprostenol if you are allergic to epoprostenol or any of the other ingredients of this medicine (listed in section 6) if you have heart failure if you start to develop a build-up of fluid in your lungs causing breathlessness after starting this treatment. If you think any of these apply to you, don't use Epoprostenol until you have checked with your doctor.
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Warnings and precautions Talk to your doctor before treatment with Epoprostenol if you bleed easily (for example from your nose). Skin damage at the injection site Epoprostenol is injected into a vein. It is important that the medicine does not leak out of the vein into the surrounding tissue. If it does, the skin could be damaged. The symptoms of this are: tenderness burning stinging swelling redness. This may be followed by blistering and shedding of the skin. While you are being treated with Epoprostenol, it is important that you check the injection area. Contact the hospital immediately for advice if the area becomes sore, painful or swollen or you notice any blistering or shedding of the skin. Effect of Epoprostenol on blood pressure and heart rate Epoprostenol can cause your heart to beat faster or slower. Also your blood pressure can become too low. While you are being treated with Epoprostenol your heart rate and blood pressure will be checked. The symptoms of low blood pressure include dizziness and fainting. Tell your doctor immediately if you get these symptoms. Your dose may need to be reduced or your infusion stopped. Children and adolescents The safety and efficacy of Epoprostenol in children have not yet been established. Other medicines and Epoprostenol Tell your doctor or nurse if you are using, have recently used or might use any other medicines. Some medicines may affect how Epoprostenol works, or make it more likely that you'll have side effects. Epoprostenol can also affect how some other medicines work if taken at the same time. These include: medicines used to treat high blood pressure medicines used to prevent blood clots medicines used to dissolve blood clots medicines to treat inflammation or pain (also called 'NSAIDs'), for example ibuprofen digoxin (used to treat heart disease). Tell your doctor or nurse if you are taking any of these. Pregnancy and breast-feeding If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before treatment with this medicine. It is not known whether the ingredients of Epoprostenol can pass into breast-milk. You should stop breastfeeding your child during treatment with Epoprostenol. Driving and using machines Your treatment may have an effect on the ability to drive or use machinery. Don't drive or use machines if you're feeling unwell.
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Epoprostenol contains sodium This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodiumfree'. The diluted solution of Epoprostenol (pH 12) must not be used with administration materials containing polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG).
3.
How to take it
Epoprostenol
Always use this medicine exactly as your doctor, nurse or pharmacist has told you. Check with your doctor or nurse if you are not sure. Epoprostenol comes as a powder in a small glass vial. The powder needs to be dissolved before use. Epoprostenol should not be given as a quick injection into your vein. It should always be given as an intravenous infusion (drip). Your doctor will decide how much Epoprostenol is right for you. The amount you are given is based on your body weight, and your type of illness. Your dose may be increased or decreased depending on how well you respond to treatment. Epoprostenol is given by slow infusion (drip) into a vein. Pulmonary arterial hypertension Your first treatment will be given to you in a hospital. This is because your doctor needs to monitor you and find the best dose for you. You will start with an infusion of Epoprostenol. The dose will be increased until your symptoms are relieved and any side effects are manageable. Once the best dose has been found, a permanent tube (line) will be fitted into one of your veins. You can then be treated using an infusion pump. Kidney dialysis You will be given an infusion of Epoprostenol for the duration of your dialysis. Using Epoprostenol at home (only for treatment of pulmonary arterial hypertension) If you are treating yourself at home, your doctor or nurse will show you how to prepare and use Epoprostenol. They will also advise you how to stop treatment if necessary. Stopping Epoprostenol must be done gradually. It is very important that you follow all their instructions carefully. Epoprostenol comes as a powder in a glass vial. Before use, the powder needs to be dissolved in a liquid. The liquid does not contain a preservative. If you have any of the liquid left over, it must be thrown away. Looking after the injection line If you have been fitted with a 'line' into a vein it is very important to keep this area clean, otherwise you could get an infection. Your doctor or nurse will show you how to clean your 'line' and the area around it. It is very important that you follow all of their instructions carefully. It is also very important that you carefully follow all instructions regarding the change of the pump drug delivery reservoir (cassette) and that you always use an extension set with an in-line filter, as instructed by your doctor to reduce the risk of an infection. If you use more Epoprostenol than you should Seek urgent medical attention if you think you have used or been given too much Epoprostenol. Symptoms of overdose may include headache, nausea, vomiting, fast heart rate, warmth or tingling, or
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feeling like you might pass out (feeling faint/dizziness). If you forget to use Epoprostenol Do not use a double dose to make up for a forgotten dose. If you stop using Epoprostenol Stopping Epoprostenol must be done gradually. If the treatment is stopped too quickly you may get serious side effects, including dizziness, feeling weak and breathing difficulties. If you have problems with the infusion pump or an injection line that stops or prevents treatment with Epoprostenol, contact your doctor, nurse or hospital immediately. If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.
4.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them. Tell your doctor or nurse immediately if you get any of the following signs of infection of the blood, low blood pressure or serious bleeding: You feel that your heart is beating faster, or you have chest pain or shortness of breath You feel dizzy or feel faint, especially on standing You have fevers or chills You have more frequent or longer periods of bleeding, for example nose bleeding The injection site becomes sore, painful or swollen or you notice any blistering or shedding of the skin (see Section 2). Other possible side effects Very common (may affect more than 1 in 10 people) headache jaw pain pain being sick (vomiting) feeling sick (nausea) diarrhoea redness of your face (flushing). Common (may affect up to 1 in 10 people) infection of the blood (septicaemia) heart beating faster slow heart beat low blood pressure bleeding at various sites and bruising more easily than normal, for example from the nose or gums stomach discomfort or pain chest pain joint pain feeling anxious, feeling nervous rash pain at the injection site decrease in the number of blood platelets (cells that help the blood to clot). This may show up in blood tests.
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Uncommon (may affect up to 1 in 100 people) sweating dry mouth. Rare (may affect up to 1 in 1000 people) infection at the injection site. Very rare (may affect up to 1 in 10,000 people) feeling of tightness around the chest feeling tired, weak feeling agitated pale skin redness at the injection site overactive thyroid gland blockage of the injection catheter. Not known (frequency cannot be estimated from the available data) enlarged or overactive spleen build up of fluid in the lungs (pulmonary oedema) increase in sugar (glucose) in the blood swelling due to build up of fluid around the stomach too much pumping of blood from the heart leading to shortness of breath, fatigue, swelling of the legs and abdomen due to fluid build-up, persistent cough. Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.
5.
How to store it
Epoprostenol
Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date, which is stated on the vial label and carton after EXP. The expiry date refers to the last day of that month. Do not freeze. Keep the vial in the outer carton in order to protect from light. The reconstituted solution should be further diluted to the final concentration within one hour of reconstitution (see Information intended for medical or healthcare professionals). For storage conditions after reconstitution and dilution of the medicine see Information intended for medical or healthcare professionals. Do not use this medicine if you notice any particles in the reconstituted solution. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
6.
Contents of the pack and other information
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What Epoprostenol contains Epoprostenol 0.5 mg, powder for solution for infusion: The active substance is epoprostenol (as epoprostenol sodium). Each vial contains 0.531 mg epoprostenol sodium equivalent to 0.5 mg epoprostenol. One ml of reconstituted solution contains 0.1 mg epoprostenol (as epoprostenol sodium). Epoprostenol 1.5 mg, powder for solution for infusion: The active substance is epoprostenol (as epoprostenol sodium). Each vial contains 1.593 mg epoprostenol sodium equivalent to 1.5 mg epoprostenol. One ml of reconstituted solution contains 0.3 mg epoprostenol (as epoprostenol sodium). The other ingredients are glycine, sucrose and sodium hydroxide (for pH adjustment).
What Epoprostenol looks like and contents of the pack White to off-white powder in a clear glass vial with a rubber stopper and an aluminium flip-off cap. Each pack contains one vial holding 0.5 mg powder. Each pack contains one vial holding 1.5 mg powder. Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp The Netherlands
This medicine is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names: Italy Epoprostenolo SUN Netherlands Epoprostenol SUN Spain Epoprostenol SUN United Kingdom (Northern Ireland) Epoprostenol This leaflet was last revised in December 2021
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———————————————————————————————————————–The following information is intended for medical or healthcare professionals only: Renal dialysis There is one pack available for use in the treatment of renal dialysis, as follows: One 0.5 mg powder vial. Reconstitution: Withdraw 5 ml of either sterile water for injection or sodium chloride 0.9% injection diluent into a sterile syringe, inject the contents of the syringe into the vial containing Epoprostenol and shake gently until the powder has dissolved. The reconstituted solution should be examined prior to further dilution. Its use is forbidden in the presence of discolouration or particles. Any unused reconstituted solution should be disposed of in accordance with local requirements. Dilution: The reconstituted solution should be further diluted to the final concentration within one hour of reconstitution. Further dilution should be performed with the same diluent as used for reconstitution of the sterile, lyophilised powder. When the Epoprostenol lyophilisate is reconstituted with sterile water for injection or sodium chloride 0.9% injection diluent, the final injection solution has a pH comprised between 11.5 and 12.
Calculation of infusion rate: Infusion rates may be calculated using the following formula: Infusion rate (ml/min) =
Dosage (ng/kg/min) × bodyweight (kg) Concentration of solution (ng/ml)
Infusion rate (ml/h) = Infusion rate (ml/min) × 60
Pulmonary arterial hypertension There are two packs available for use in the treatment of pulmonary arterial hypertension, as follows: One 0.5 mg powder vial. One 1.5 mg powder vial. Reconstitution: Withdraw 5 ml of either sterile water for injection or sodium chloride 0.9% injection diluent into a sterile syringe, inject the contents of the syringe into the vial containing Epoprostenol and shake gently until the powder has dissolved. The reconstituted solution should be examined prior to further dilution. Its use is forbidden in the presence of discolouration or particles. Any unused reconstituted solution should be disposed of in accordance with local requirements. Dilution: The reconstituted solution should be further diluted to the final concentration within one hour of reconstitution. Further dilution should be performed with the same diluent as used for reconstitution of the sterile, lyophilised powder. Epoprostenol when administered chronically, should be prepared in a drug delivery reservoir appropriate for the infusion pump. When the Epoprostenol lyophilisate is reconstituted with sterile water for injection or sodium chloride 0.9% injection diluent, the final injection solution has a pH comprised between 11.5 and 12.
Suitable ambulatory pumps to be used for the administration of Epoprostenol include: –
CADD-Legacy 1 CADD-Legacy PLUS
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Manufactured by Smiths Medical. Pump accessories found to be compatible with the administration of Epoprostenol include: –
CADD disposable Medication Cassette Reservoir 50 mL; 100 mL from Smiths Medical. CADD extension set with in-line 0.2 micron filter (CADD extension set with male luer, 0.2micron air-eliminating filter, clamp, and integral anti-siphon valve with male luer) from Smiths Medical.
Only extension sets with an in-line 0.22 micron filter placed between the infusion pump and the catheter must be used. It is recommended to use filters with a hydrophilic polyethersulfone membrane. The extension set and the in-line filter must be changed at least every 48 hours. The diluted solution of Epoprostenol (pH 12) must not be used with administration materials containing polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG). The vial containing 0.5 mg epoprostenol must be used for the preparation of solutions with final concentrations below 15,000 ng/mL. Table 1 provides examples for preparing frequently used concentrations of Epoprostenol solutions. Each vial is for single use only. Table 1: Frequently used concentrations – Examples of reconstitution and dilution Final Concentration (ng/ml) 3000 ng/ml
Directions:
Dissolve contents of one 0.5 mg vial with 5 ml of either sterile water for injection or sodium chloride 0.9% injection. Withdraw 3 ml of the vial contents and add to a sufficient volume of the identical diluent to make a total of 100 ml. 5000 ng/ml Dissolve contents of one 0.5 mg vial with 5 ml of either sterile water for injection, or sodium chloride 0.9% injection. Withdraw entire vial contents and add to a sufficient volume of the identical diluent to make a total of 100 ml. 10,000 ng/ml Dissolve contents of two 0.5 mg vials, each with 5 ml of either sterile water for injection or sodium chloride 0.9% injection. Withdraw entire vial contents and add to a sufficient volume of the identical diluent to make a total of 100 ml. 15,000 ng/ml* Dissolve contents of one 1.5 mg vial with 5 ml of either sterile water for injection or sodium chloride 0.9% injection. Withdraw entire vial contents and add to a sufficient volume of the identical diluent to make a total of 100 ml. 30,000 ng/ml* Dissolve contents of two 1.5 mg vials, each with 5 ml of either sterile water for injection or sodium chloride 0.9% injection. Withdraw entire vial contents and add to a sufficient volume of the identical diluent to make a total of 100 ml. 30,000 ng/ml* Dissolve contents of one 1.5 mg vial with 5 ml of either sterile water for injection or sodium chloride 0.9% injection. Withdraw entire vial contents and add to a sufficient volume of the identical diluent to make a total of 50 ml. * Solutions with higher final concentrations may be necessary for patients who receive longterm administration of Epoprostenol.
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Epoprostenol diluted to the final concentration in the drug delivery reservoir as directed can be administered immediately at room temperature (25oC) or, if stored, for up to 8 days at 2 to 8oC as per the conditions of use outlined in Table 2. Table 2: Maximum duration of administration (hours) at room temperature (25oC) of fully diluted solutions stored in the drug delivery reservoir Final concentration range ≥ 3000 ng/ml and <15,000 ng/ml ≥ 15,000 ng/ml
Immediate administration* 48 hours 48 hours
If stored for up to 8 days at 2 to 8oC* 24 hours 48 hours
Do not expose the fully diluted solution to direct sunlight. Special precautions for storage Do not freeze. The reconstituted solution should be further diluted to the final concentration within one hour of reconstitution. Reconstitution and dilution should be carried out immediately prior to use. Freshly prepared epoprostenol diluted solutions for the treatment of pulmonary arterial hypertension can be administered immediately at 25°C, or stored in the drug delivery reservoir in order to protect from light for up to 8 days at 2 to 8°C as per the conditions of use outlined in Table 2.
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Frequently asked questions about Epoprostenol 1.5 mg powder for solution for infusion
How do I take Epoprostenol 1.5 mg powder for solution for infusion?
Epoprostenol 1.5 mg powder for solution for infusion comes as infusion containing 1.5mg. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
What is the active substance in Epoprostenol 1.5 mg powder for solution for infusion?
The active substance in Epoprostenol 1.5 mg powder for solution for infusion is epoprostenol sodium.
Are there equivalent medicines to Epoprostenol 1.5 mg powder for solution for infusion?
Medicines with the same active substance, strength and form include: Flolan 1.5 mg Powder and Solvent for Solution for Infusion (with pH 12 solvent & Vented Vial Adaptor), Veletri 1.5mg; Powder for Solution for Infusion. They are interchangeable only if your prescriber or pharmacist says so.
Where does this information come from?
This leaflet reproduces the patient information leaflet approved for Epoprostenol 1.5 mg powder for solution for infusion, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Can I get Epoprostenol 1.5 mg powder for solution for infusion without a prescription?
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
About this leaflet
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
- Source: electronic medicines compendium (emc), Datapharm
- Active substance: epoprostenol sodium
- Official document: view the original leaflet on emc →
⚕For healthcare professionals — Summary of Product Characteristics (SmPC)Full SmPC: dosage, interactions, contraindications, warnings+
4.1. Therapeutic indications
Epoprostenol is indicated for:
Pulmonary arterial hypertension
Epoprostenol is indicated for the treatment of pulmonary arterial hypertension (PAH) (idiopathic or heritable PAH and PAH associated with connective tissue diseases) in patients with WHO Functional Class III–IV symptoms to improve exercise capacity (see section 5.1).
Renal dialysis
Epoprostenol is indicated for use in haemodialysis in emergency situations when use of heparin carries a high risk of causing or exacerbating bleeding or when heparin is otherwise contraindicated (see section 5.1).
4.2. Posology and method of administration
Posology
Pulmonary arterial hypertension
Epoprostenol is only indicated for continuous infusion by intravenous route.
Treatment should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension.
Short-term (acute) dose ranging
This procedure should be conducted in a hospital with adequate resuscitation equipment.
A short-term dose-ranging procedure administered via either a peripheral or central venous line is required to determine the long-term infusion rate. The infusion rate is initiated at 2 nanograms/kg/min and increased by increments of 2 nanograms/kg/min every 15 min or longer until maximum haemodynamic benefit or dose-limiting pharmacological effects are elicited.
If the initial infusion rate of 2 nanograms/kg/min is not tolerated, a lower dose which is tolerated by the patient should be identified.
Long-term continuous infusion
Long-term continuous infusion of epoprostenol should be administered through a central venous catheter. Temporary peripheral i.v. infusions may be used until central access is established. Long-term infusions should be initiated at 4 nanograms/kg/min less than the maximum tolerated infusion rate determined during short-term dose-ranging. If the maximum tolerated infusion rate is 5 nanograms/kg/min or less, then the long-term infusion should be started at 1 nanogram/kg/min.
Dosage adjustments
Changes in the long-term infusion rate should be based on persistence, recurrence or worsening of the patient's symptoms of pulmonary arterial hypertension or the occurrence of adverse reaction due to excessive doses of epoprostenol.
In general, the need for increases in dose from the initial long-term dose should be expected over time. Increases in dose should be considered if symptoms of pulmonary arterial hypertension persist, or recur after improving. The infusion rate should be increased by 1 to 2 nanograms/kg/min increments at intervals sufficient to allow assessment of clinical response; these intervals should be of at least 15 min. Following establishment of a new infusion rate, the patient should be observed, and erect and supine blood pressure and heart rate monitored for several hours to ensure that the new dose is tolerated.
During long-term infusion, the occurrence of dose-related pharmacological events similar to those observed during the dose-ranging period may necessitate a decrease in infusion rate, but the adverse reactions may occasionally resolve without dosage adjustment. Dosage decreases should be made gradually in 2 nanograms/kg/min decrements every 15 min or longer until the dose-limiting effects resolve. Abrupt withdrawal of epoprostenol or sudden large reductions in infusion rates should be avoided due to the risk of potential fatal rebound effect (see section 4.4). Except in lifethreatening situations (e.g. unconsciousness, collapse, etc) infusion rates of epoprostenol should be adjusted only under the direction of a physician.
Renal dialysis
Epoprostenol is suitable for continuous infusion only, either intravascularly or into the blood supplying the dialyser.
The following schedule of infusion has been found effective in adults:
Prior to dialysis: 4 nanograms/kg/min intravenously for 15 mins.
During dialysis: 4 nanograms/kg/min into the arterial inlet of the dialyser.
The infusion should be stopped at the end of dialysis.
The recommended dose for renal dialysis should be exceeded only with careful monitoring of patient blood pressure.
Elderly
There is no specific information on the use of epoprostenol in patients over 65 years for pulmonary arterial hypertension or renal dialysis. In general, dose selection for an elderly patient should be made carefully, reflecting the greater frequency of decreased hepatic, renal (in the case of pulmonary arterial hypertension) or cardiac function and of concomitant disease or other medicine therapy.
Paediatric population
The safety and efficacy of epoprostenol in children younger than 18 years have not yet been established.
Method of administration
Epoprostenol long-term administration is administered via intravenous route through central venous catheter using an ambulatory infusion pump. The patient must be adequately trained in all aspects of care of the central venous catheter, in the aseptic preparation of the epoprostenol intravenous injectable solution, and in the preparation and change of the drug delivery reservoir of the infusion pump, and the extension set.
Suitable ambulatory pumps to be used for the administration of Epoprostenol are provided in section 6.6.
Reduction of the risk of catheter-related blood-stream infection
Particular attention should be given to the recommendations in section 4.4 and the following as this should help to reduce the risk of catheter-related blood-stream infections.
The care of the central venous catheter and the catheter exit site should follow established medical principles.
Only extension sets with an in-line 0.22 micron filter placed between the infusion pump and the central venous catheter must be used. It is recommended to use filters with a hydrophilic polyethersulfone membrane. The extension set and the in-line filter must be changed at least every 48 hours (see section 6.6).
Preparation of epoprostenol intravenous injectable solution
The reconstituted solution should be examined prior to further dilution. Its use is forbidden in the presence of discolouration or particles. Reconstituted solutions should be further diluted to the final concentration within one hour of reconstitution.
For further instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.
Epoprostenol must not be administered as a bolus injection.
4.3. Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Congestive heart failure arising from severe left ventricular dysfunction
Epoprostenol must not be used chronically in patients who develop pulmonary oedema during dose-ranging.
4.4. Special warnings and precautions for use
The pH of the diluted “ready-to-use solution” decreases with dilution, and ranges from 12.0 for a concentration of 90,000 ng/ml, 11.7 for a concentration of 45,000 ng/ml to 11.0 for a concentration of 3,000 ng/ml. Therefore, peripheral intravenous use should be restricted to short duration only, using low concentrations.
Because of the high pH of the final infusion solutions, care should be taken to avoid extravasation during their administration and consequent risk of tissue damage.
Epoprostenol is a potent pulmonary and systemic vasodilator. The cardiovascular effects during infusion disappear within 30 min of the end of administration.
Epoprostenol is a potent inhibitor of platelet aggregation, therefore, an increased risk for haemorrhagic complications should be considered, particularly for patients with other risk factors for bleeding (see section 4.5).
If excessive hypotension occurs during administration of epoprostenol, the dose should be reduced or the infusion discontinued. Hypotension may be profound in overdose and may result in loss of consciousness (see section 4.9).
Blood pressure and heart rate should be monitored during administration of epoprostenol.
Epoprostenol may either decrease or increase heart rate. The change is thought to depend on both the basal heart rate and the concentration of epoprostenol administered.
The effects of epoprostenol on heart rate may be masked by concomitant use of drugs which affect cardiovascular reflexes.
Extreme caution is advised in patients with coronary artery disease.
Elevated serum glucose levels have been reported (see section 4.8).
This medicine contains less than 1 mmol sodium (23 mg) per maximum daily dose, that is to say essentially 'sodium- free'.
Pulmonary arterial hypertension
Some patients with pulmonary arterial hypertension have developed pulmonary oedema during dose-ranging, which may be associated with pulmonary veno-occlusive disease. Epoprostenol must not be used chronically in patients who develop pulmonary edema during dose initiation (see section 4.3).
Abrupt withdrawal or interruption of infusion must be avoided, except in life-threatening situations. An abrupt interruption of therapy can induce a rebound of pulmonary arterial hypertension resulting in dizziness, asthenia, increase dyspnoea, and may lead to death (see section 4.2).
Epoprostenol is infused continuously through a permanent indwelling central venous catheter via a small, portable infusion pump. Thus, therapy with epoprostenol requires commitment by the patient to sterile drug reconstitution, drug administration, care of the permanent central venous catheter, and access to intense and ongoing patient education.
Sterile technique must be adhered to in preparing the drug and in the care of the catheter. Even brief interruptions in the delivery of epoprostenol may result in rapid symptomatic deterioration. The decision to administer epoprostenol for pulmonary arterial hypertension should be based upon the patients understanding that there is a high likelihood that therapy with epoprostenol will be needed for prolonged periods, possibly years, and the patient's ability to accept and care for a permanent i.v. catheter and infusion pump should be carefully considered.
Renal dialysis
The hypotensive effect of epoprostenol may be enhanced by the use of acetate buffer in the dialysis bath during renal dialysis.
During renal dialysis with epoprostenol, it should be ensured that the cardiac output increases more than minimally so that delivery of oxygen to peripheral tissue is not diminished.
Epoprostenol is not a conventional anticoagulant. Epoprostenol has been successfully used instead of heparin in renal dialysis but in a small proportion of dialyses clotting has developed in the dialysis circuit, requiring termination of dialysis. When epoprostenol is used alone, measurements such as activated whole blood clotting time may not be reliable.
4.5. Interaction with other medicinal products and other forms of interaction
When epoprostenol is administered to patients receiving concomitant anticoagulants standard anticoagulant monitoring is advisable.
The vasodilator effects of epoprostenol may augment or be augmented by concomitant use of other vasodilators.
As reported with other prostaglandin analogues, epoprostenol may reduce the thrombolytic efficacy of tissue plasminogen activator (t-PA) by increasing hepatic clearance of t-PA.
When NSAIDS or other drugs affecting platelet aggregation are used concomitantly, there is the potential for epoprostenol to increase the risk of bleeding.
Patients on digoxin may show elevations of digoxin concentrations after initiation of therapy with epoprostenol which although transient, may be clinically significant in patients prone to digoxin toxicity.
4.6. Fertility, pregnancy and lactation
Pregnancy
There are no or limited amount of data from the use of epoprostenol in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).
Given the absence of alternative medicinal products, epoprostenol can be used in those women who choose to continue their pregnancy, despite the known risk of pulmonary arterial hypertension during pregnancy.
Breast-feeding
It is unknown whether epoprostenol or its metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with epoprostenol.
Fertility
There are no or limited data on the effects of epoprostenol on fertility in humans. Reproductive studies in animals have shown no effects on fertility (see section 5.3).
4.7. Effects on ability to drive and use machines
Pulmonary arterial hypertension and its therapeutic management may affect the ability to drive and operate machinery.
There are no data regarding the effect of epoprostenol used in renal dialysis on the ability to drive or operate machinery.
4.8. Undesirable effects
Adverse events are listed in the following table by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥ 1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥ 1/10,000 to <1/1000), very rare (<1/10,000) and not known (cannot be estimated from the available data).
Infections and Infestations
Common
Sepsis, septicaemia (mostly related to delivery system for epoprostenol)1
Blood and Lymphatic System Disorders
Common
Decreased platelet count, bleeding at various sites (e.g. pulmonary, gastrointestinal, epistaxis, intracranial, post-procedural, retroperitoneal)
Not known
Splenomegaly, hypersplenism
Endocrine Disorders
Very rare
Hyperthyroidism
Psychiatric Disorders
Common
Anxiety, nervousness
Very rare
Agitation
Nervous System Disorders
Very common
Headache
Cardiac Disorders
Common
Tachycardia2, bradycardia3
Not known
High output cardiac failure
Vascular Disorders
Very common
Facial flushing (seen even in the anaesthetised patient)
Common
Hypotension
Very rare
Pallor
Not known
Ascites
Respiratory, Thoracic and Mediastinal Disorders
Not known
Pulmonary oedema
Gastrointestinal Disorders
Very common
Nausea, vomiting, diarrhoea
Common
Abdominal colic, sometimes reported as abdominal discomfort
Uncommon
Dry mouth
Skin and Subcutaneous Tissue Disorders
Common
Rash
Uncommon
Sweating
Musculoskeletal and Connective Tissue Disorders
Very common
Jaw pain
Common
Arthralgia
General Disorders and Administration Site Conditions
Very common
Pain (unspecified)
Common
Pain at the injection site*, chest pain
Rare
Local infection*
Very rare
Erythema over the infusion site*, occlusion of the long i.v. catheter*, lassitude, chest tightness
Investigations
Not known
Blood glucose increased
* Associated with the delivery system for epoprostenol
1 Cathether-related infections caused by organisms not always considered pathogenic (including micrococcus) have been reported.
2 Tachycardia has been reported as a response to epoprostenol at doses of 5 nanograms/kg/min and below.
3 Bradycardia, sometimes accompanied by orthostatic hypotension, has occurred in healthy volunteers at doses of epoprostenol greater than 5 nanograms/kg/min. Bradycardia associated with a considerable fall in systolic and diastolic blood pressure has followed i.v. administration of a dose of epoprostenol equivalent to 30 nanograms/kg/min in healthy conscious volunteers.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9. Overdose
The main feature of overdose is likely to be hypotension.
In general, events seen after overdose of epoprostenol represent exaggerated pharmacological effects of the drug (e.g. hypotension and complications of hypotension).
If overdose occurs reduce the dose or discontinue the infusion and initiate appropriate supportive measures as necessary; for example plasma volume expansion and/or adjustment to pump flow.
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